Adjuvant Chemotherapy in Resected Rectal Cancer

Primary Recommendation

The National Comprehensive Cancer Network recommends adjuvant chemotherapy for all patients with stage II/III rectal cancer after neoadjuvant chemoradiotherapy and surgery, with FOLFOX or CAPEOX as preferred regimens for higher-risk patients and 5-FU/LV or capecitabine as acceptable alternatives for lower-risk patients who responded well to neoadjuvant fluoropyrimidine-based therapy 1, 2

The evidence supporting adjuvant chemotherapy in rectal cancer is notably weaker than in colon cancer, creating a challenging clinical scenario, and the NCCN panel recommends adjuvant therapy use based on the totality of available evidence 2, 3
The ADORE trial demonstrated improved 3-year disease-free survival (DFS) with adjuvant FOLFOX versus 5-FU/LV (71.6% vs 62.9%; HR 0.66, P=0.047) 3, 4
The CAO/ARO/AIO-04 trial showed improved 3-year DFS when oxaliplatin was added to 5-FU in both neoadjuvant and adjuvant settings (75.9% vs 71.2%; P=0.03) 3, 4
NCDB analyses of patients achieving pathologic complete response (pCR) found significant overall survival improvement with adjuvant chemotherapy 3, 5

The choice of adjuvant regimen depends on initial clinical staging and predicted circumferential resection margin (CRM) status 2, 3
For higher-risk patients, FOLFOX or CAPEOX are preferred regimens 8
For lower-risk patients, 5-FU/LV or capecitabine are acceptable alternatives 1, 2, 3

Adjuvant chemotherapy should be initiated as soon as the patient is medically able after surgery, as each 4-week delay results in a 14% decrease in overall survival 2, 8, 10
The recommended duration of adjuvant chemotherapy is 4 months of FOLFOX when preoperative chemoradiotherapy is administered 2, 8

For patients with pathologic complete response (pCR), adjuvant chemotherapy is still recommended despite excellent outcomes in observational studies 3, 4, 11
For stage III rectal cancer with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), immunotherapy with dostarlimab is preferred over standard total neoadjuvant therapy 7

Only 61.5% to 76.6% of eligible patients receive adjuvant chemotherapy in real-world settings 2, 5
Factors associated with not receiving adjuvant therapy include complete pathologic response, infection, advanced age, poor performance status, and socioeconomic factors 2, 3, 5
Oxaliplatin-induced peripheral neuropathy is cumulative and dose-limiting; monitor closely and consider dose reduction or discontinuation if grade 2-3 neuropathy develops 7